Psoralen plus long wavelength ultraviolet radiation (UV-A) is being investigated as a model system for clinically relevant photochemical carcinogenesis. Used experimentally for treatment of psoriasis and mycosis fungoides, psoralen plus UV-A has been found to be mutagenic and carcinogenic. We have developed an in vitro assay to measure the effects of UV-A mediated psoralen-DNA binding on human lymphoid cells. Parameters monitored include the rate of DNA synthesis, induction of DNA-psoralen cross-links, induction of sister chromatid exchanges, alterations in the rate of cell proliferation and survival and in immune reactivity. These studies indicate that the low doses of psoralen plus UV-A received by patients' leukocytes during therapy may result directly in decreased DNA synthesis in their circulating lymphoid cells. Presently, we are investigating whether lymphoid cells from patients with cancer-prone genetic diseases have increased sensitivity to cell killing and mutagenesis induced by psoralen plus UV-A. These studies are aimed at understanding the mechanism of cell damage induced by psoralen plus UV-A so as to minimize the toxicity to human cells during therapy and to identify individuals with abnormal sensitivity.